19-bisdifluoro-pregnanes



United States. Patent Office 3,257,389 Patented June 21, 1966 3,257,38919-BISDIFLUOR0-PREGNANES Albert Bowers and James C. Orr, Mexico City,Mexico, assignors to Syntex Corporation, Panama, Panama, a corporationof Panama N Drawing. Filed Sept. 21, 1962, Ser. No. 225,364 29 Claims.(Cl. 260-23955) The present invention relates to novelcyclopentanophenanthrene derivatives and to a process for the productionthereof.

More particularly, the present invention relates to novel 19,19-difluoropregnane derivatives.

The novel compounds of the present invention are rep- In the aboveformulae X represents hydrogen, fluorine or chlorine all having ocorti-configurations; R represents hydrogen, hyd-roxyl or a hydrocarboncarboxylic acyloxy group of less than 12 carbon atoms; T representshydrogen, OL-hYdI'OXYl, a-acyloxy, a-methyi' or fi-methyl; T and Rtogether represent the group at the 16a,17x-position, wherein R and Reach represents a lower alkyl group; Z represents a double bond or asaturated linkage between 0-1 and C2, and R represents a hydrogen or ahydrocarbon carboxylic acyl group of less than 12 carbon atoms.

The acyl and acyloxy groups are derived from hydrocarbon carboxylicacids containing less than 12 carbon atoms which may be saturated orunsaturated, of straight, branched, cyclic or cyclic-aliphatic chain,aromatic and may be substituted by functional groups such as hydroxy,alkoxy containing up to 5 carbon atoms, acyloxy containing up to 12carbon atoms, nitro, amino or halogen. Typical ester groups are theacetate, propionate, enanthate, benzoate, trimethylacetate,t-butylacetate', phenoxyacetate, cyclopentylpropionate, aminoacetate,and fi-chloropropionate.

The compounds represented by the above formulae are powerfulprogestational agents with good oral activity. In addition they haveanti-androgenic, anti-gonadotrophic and anti-estrogenic properties andare useful in fertility control, furthermore they may be used in thetreatment of pre-menstrual tension.

The novel compounds of the present invention are prepared by the processexemplified as follows:

Ho H20 I p a00- (EH3 CIHS "u-R! -----R OHC F1110 0 (III) (I311; CH3 o=o=0 E (W) 0: (W)

CH3 CH3 3:0 (i=0 1...

In the above formulae R, T, X, Z and R have the same meaning asdescribed previously; R represents hydrogen ora hydrocarbon carboxylicacyl group of less than 12 carbon atoms; T represents hydrogen,a-acyloxy, (It-methyl or 8-methyl; T and R together represent the groupwherein R and R have the same meaning as set forth hereinbefore.

The starting compound (I) of the above exemplified process which is a3-acyloxy-l9-hydrOXy-ZO-ketO-A -pregnene derivative, is obtained inaccordance with US. Patent No. 3,065,228 to Bowers, by treatment of thecorresponding 3-acyloXy-A -pregnene with hypobromous, acid,

to give the corresponding 3-acyloxy-5u-bromo-6,B-hydroxy-pregnane,reacting the latter with lead tetraacetate to produce the corresponding3-acyloxy-5a-br0mo-6/8,19- oxido-pregnene derivative and finallytreating the latter compound with zinc in a lower aliphatic alcohol.

In practicing the process outlined above the starting compound (I) isoxidized, preferably with chromium trioxide in pyridine, thus giving thecorresponding A -pregnen-35-ol-19-al-20-one acylate (II), which upontreat ment with approximately 2 molar equivalents of sulfurtetrafluoride in a sealed vessel, at approximately 0-50 C., for aprolonged period of time of the order of 6 to 14 days, preferably during8 days, yields the corresponding l9,19-difluoro-A -pregnen-3/8-ol-2O-oneacylate (III: R =acyl). Conventional saponification of the acyloxy groupof the latter derivative affords the corresponding free 3fi-alcohol(III: R =H). The latter compound having the remaining hydroxyl groupspresent protected (III: R=R T=T is treated under conventional Oppenauerconditions to give the corresponding 19,19-difluoro- A-pregnene-3,20-dione derivative (IV). The latter compound upon treatmentwith ethyl orthoformate in the presence of p-toluenesulfonic acidaffords the corresponding 19,19-difluoro-3-ethoxy-A -pregnadien--onewhich is treated with approximately 1 molar equivalent of N- chlorosuccinimide or another N-chloro amide or imide, in the presence ofacetic acid and sodium acetate, or with perchlorylfluoride, indimethylformamide, thus affording respectively the corresponding6,8-chloro-19,19-difluoro- A -pregnene 3,20 dione and6,8,19,19-trifluoro-A -pregnene-3,20-dione (V: X=B-fiuoro or ,B-chloro).

The {i-halo group of the latter compound is epimerized in an acid mediumsuch as hydrogen chloride in acetic acid, to give the corresponding6u-halo derivatives (V: X=wfll10f0 or ot-chloro). The 19,19-difluoro-A-3,20- dione derivative of the present invention (IV, V) upon reactionwith chloranil in xylene or t-butanol at reflux temperature for a periodof time between 8 and 16 hours produced the corresponding A -derivatives(VII: Z: saturated linkage).

The 19,19-difluoro-A -pregnene-3,20-dione derivatives of the presentinvention (IV, V) are treated with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in a suitable sol- Vent, such asdioxane, preferably at reflux temperature for a period of timeof 10hours to produce the corresponding A -pregnadiene derivatives (VI). Whenthe aforementioned A -derivatives are treated under the same conditions,there are obtained the corresponding A -pregnatriene compounds (VII:Z=double bond).

The compounds of the present invention having a 160;, 17oc-k6t0nidegrouping produce the corresponding 16a, 17ot-diOls by conventionaltreatment with a strong acid, such as formic acid. The obtained diols,upon conventional esterification in pyridine, with an -acylation agent,such as for example acetic anhydride or caproic anhydride, produce thecorresponding 16-acylates.

The compounds of the present invention having a 17cchydroxy group areconventionally acylated in the presence of p-toluenesulfonic acid withan acylating agent such as an anhydride of a hydrocarbon carboxylic acidof the type disclosed hereinbefore to give the corresponding17x-acylates.

The following specific examples serve to illustrate but are not intendedto limit the scope of the present invent1on: I

EXAMPLEI Crys- 4 tallization from acetone-hexane afforded A-pregnene-3fiol-l9-al-20-one acetate (Compound No. 1).

Following the some procedure, the starting compounds listed under I(obtained in accordance with US. Patent No. 3,065,228 to Bowers andcopending application Serial No. 194,717, filed May 14, 1962 now US.Patent No. 3,124,574) were respectively converted into the products setforth under II.

I Cpd. II

lfitz-methyl-A -pregnene- 2 IGa-Inethyl-A -pregnene- 36,19-diol-20-one3acetate. 35-01-19-a1-20-0ne acetate. lfifi-methyl-A -pregnene- 316fl-methyl-A -pregnene- 36,19-di0l-20-0ne 3-acetate.3fl-ol-19-al-20-one acetate. 16a, 17a-isopropylidene- 416a,17a-isopropylidenedioxy-N-pregnene-SBJQ-dioxy-N-pregnene-BB-oldiol-ZO-one 3-acetate.

19-al-20-one acetate.

A -pregnene-3B,17a,19-triol- -5 A -pregnene-3B,17a-di0l-19- 20-one3,17-diacetate. al-ZO-one diacetate.

lfia-methyl-A -pregnene- 6 lfia-methyLN-pregnene- 3B,l7a,19-triol-20-0ne36,17a-dio1-19-al-20-0ne 3,17-diacetatc. diacetate.

EXAMPLE II 500 mg. of A -pregnene-3fi-ol-l9-al-20-one acetate (Cpd.No. 1) were dissolved in 25 cc. of dioxane and treated at 70 C. with 2molar equivalents of sulfur tetrafluoride. The reaction vessel wassealed and the temperature permitted to attain 20 C. After 8 days, thereaction mixture was cooled and the contents of the tube pouredcarefully into ice water. An excess of sodium carbonate was added andthe product extracted with methylene chloride. The extract was washedwith water to neutral, dried and evaporated to dryness. Afterchromatography and crystallization of the solid fractions fromacetone-hexane, there was obtained 19,19-difluoro- A-pregnene-3fi-ol-20-one acetate (Cpd. No. 8).

The compounds Nos. 2 to 7, inclusive, were treated in accordance withthe above procedure, thus affording respectively-- EXAMPLE III Asuspension of 1 g. of 19,l9- difluoro-A -pregnene-3fiol-20-one acetate(Cpd. No. 8) in cc. of methanol was treated with a solution of 1 g. ofpotassium carbonate in 6 cc. of water; the mixture was boiled underreflux for 1 hour and then cooled in ice and diluted with water. Theformed precipitate was collected and recrystallized from acetone-hexaneto yield 19,19-difluoro-A -pregnene- 3fl-ol-20-one (Cpd. No. 15).

The compounds Nos. 9 to 14, inclusive, were treated in the same manner,thus giving respectively the following compounds- Cpd. No.:

16. 19,19 difluoro 16a methyl A pregnene- 3fi-ol-20-one. V 17. 19,19difluoro 16,8 methyl A pregnene- 3/3-ol-20-one.

18. 19,19 difluoro 16a,17ot isopropylidenedioxy- A-pregnene-3,8-ol-20-one.

19. 19,19 difluoro A pregnene 35,170; diol- 20-one-17-acetate. 20. 19,19difluoro 16a methyl A pregnene- 313,17a-dil-20-one 17-acetate. 21. 19,19difluoro 16$ methyl A pregnene- 3B,17ot-diol-20-one 17-acetate.

' EXAMPLE IV A solution of 1 g. of 19,19-difluoro-A -pregnene-3B-ol-20-one (Cpd. No. 15) in 80 cc. oftoluene and 20 cc. of 'cyclohexanonewas dried by distilling off cc. of the solvent. A solution of 1 g. ofaluminum isopropoxide dissolved in 7 cc. of anhydrous toluene was thenadded and the mixture was refluxed for 45 minutes; 4 cc. of acetic acidwere added and the solvents removed by steam distillation. The productwas extracted several times with ethyl acetate and the organic extractswashed with 5% hydrochloric acid solution, water, 10% sodium carbonatesolution and water until neutral, dried over anhydrous sodium sulfateand evaporated to dryness. Crystallization from acetone-hexane afforded19,19-difluoro A -pregnene-3,20-dione (Cpd. No. 22).

Following the same procedure, the compounds Nos. 16 .to 21, inclusive,were respectively transformed into Cpd. No.: 23.19,19-difluoro-16a-methyl-A -pregnene-3,20 d1- one.

24. 19,19-difluoro-16B-methyl-A -pregnene-3,20 dione.

25. 19,19-difluoro-16a,17a-isopropy1idenedioxy -A pregnene-3,20-dione.

26. 19,l9-difluoro-A pregnene-1704-01-3,20-dione acetate.

27. 19,19-difluoro-16a-methyl-A -pregnene-17a-ol 3, ZO-dione acetate.

28. 19,19-difluoro-16/3-methyl-A -pregnene-17a-ol 3, 20-dione acetate.

EXAMPLE V A mixture of 500 mg. of 19,l9-difluoro-A -pregnene-3, 20-dione(Cpd. No. 22), 10 cc. of dioxane and 350 mg. of2,3-dichloro-5,6-di-cyano-1,4 benzoquinone was refluxed for 10 hours. Itwas then cooled, the 2,3-dichloro-5,6- dicyano-1,4-benzohydroquinoneformed during the reac- .tion filtered 01f, and the filtrate evaporatedto dryness. The residue was dissolved in acetone and filtered through 10g. of alumina. Crystallization from acetone-hexane gave 19,19-difluoro-A-pregnadiene-3,20-dione (Cpd. No. 29).

Following the same procedure, the compounds Nos. 23 to 28, inclusive,were respectively transformed into .Cpd. No.:

30. 19,19-difluoro-16a-rnethyl-A -pregnadiene-3,20- dione.

31. 19,19-difluoro-16,6-methyl-A -pregnadiene-LZO- dione.

32. 19,19-difluoro-16a,17ot-isopropylidenedioxy-Apregnadiene-3,20-dione.

3 3. 19,19-difluoro-A -pregnadiene-17a-ol-3 ,ZO-dione acetate.

34. 19,19-difluoro-16a-methyl-A -pregnadiene-17aol-3,20-dione acetate.

35. 19,19-difluoro-16,8-methyl-A -pregnadiene 17aol-3,20-dicne acetate.

EXAMPLE VI A mixture of 1 g. of 19,19-difluoro-A -pregnene-3,20-dione(Cpd. No. 22), 2 g. of chloranil and 10 cc. of xylene was refluxed underan atmosphere of nitrogen for 16 hours. The mixture was cooled, washedwith a cold 10% sodium. hydroxide solution, then with water, dried overanhydrous sodium sulfate and the xylene was evaporated under reducedpressure. Chromatography of the residue on neutral alumina andrecrystallization from acetonehexane afiorded 19,19-difluoro-A-pregnadiene-3,20 dione (Cpd. No. 36). By the same procedure, CompoundNo. 27 was converted into: 19,19-difluoro-16a-methyl- A-pregnadiene-17a-ol-3,20-dione acetate (Cpd. No. 37).

EXAMPLE VII A suspension of 1 g. of 19,19-difluoro-A -pregnene-3,20-dione (Cpd. No. 22) in 7.5 cc. of anhydrous peroxidefree dioxane wastreated with 1.2 cc. of freshly distilled ethyl orthoformate and 0.8 g.of p-toluenesulfonic acid. The mixture was stirred at room temperaturefor 15 minutes and the resulting solution let stand for 30 minutesfurther. 0.8 cc. of pyridine were added and then water. The formedprecipitate was collected by filtration, water Washed and air dried.Recrystallization from acetonehexane aflorded 19,19-difluoro-3-ethoxy-A-pregnadiene- ZO-one (Cpd. N0. 38). By the same procedure, Compound No.27 was transformed into: 19,19-difluoro-16u-methyl- 3-ethoxy-A-pregnadiene-17oa-ol-20 one acetate (Cpd. No. 39).

EXAMPLE VIII A mixture of 5 g. of 19,19-difluoro-3 ethoxy -Apregnadiene-20-one (Cpd. No. 38), 2 g. of anhydrous sodium acetate andcc. of acetone was treated with 32 cc. of water and the solution wascooled to a temperature between 0 and 5 C. There was then added 1.1molar equivalents of N-chloro-succinimide and 2 cc. of glacial aceticacid and the mixture was stirred between 0 and 5 C. for 30 minutes. Itwas then diluted with water, kept overnight at 0 C. and the precipitateformed was collected, washed with water, dried under vacuum andrecrystallized from acetone, thus giving 6B-chloro- 19,19-difluoro-A-pregnene-3,2O-dione (Cpd. No. 40). By the same procedure, compound No.39 was converted into: 6fi-chloro-19,19-difluoro-16a-methyl-A pregnene-17a-ol-3,20-dione acetate (Cpd. No. 41).

EXAMPLE IX 1 g. of 19,19-difluoro-3-ethoxy-A -pregnadiene-2O-one (Cpd.No. 38) was dissolved in 25 cc. of dimethylformamide. The solution wascooled to 0 C. and a stream of perchloryl fluoride was passed for 5minutes; the solution was allowed to com slowly to 20 C.; it was thenpoured into water and extracted with ethyl acetate. The extract waswashed with saturated aqueous solution of sodium bicarbonate, then withwater to neutrality, dried over anhydrous sodium sulfate, and evaporatedto dryness. By chromatography over washed alumina .there was obtained6p,19,19-tnifluoro-A -pregnene-3,20 dione (Cpd. No. 42).

Following the same procedure, but using compound No.

' 39 as starting material, there was produced 63,19,19-tri- Into asolution of 3 g. of compound No. 40 in cc. of glacial acetic acid waspassed a slow stream of dry hydrochloric acid for 4 hours, whilemaintaining the temperature around 15 C. The mixture was then pouredinto ice-water, the precipitate collected, washed with Water, dried andrecrystallized from acetone-hexane to give 6ot-chlor-o-19,l9-difluoro Apregnene-3,20 dione (Cpd. No. 44). I

The compounds Nos. 41, 42 and 43 were treated by the same procedure,thus yielding respectively: 6a-chloro- 19,19-difluoro-l6a-methyl-A-pregnene-l7ot-ol 3,20-dione acetate (Cpd. No. 45), 6a,19,19-trifluoro-A-pregnene- 3,20-dione (Cpd. No. 46), and601,19,19-t1lfil1010l60cmethyl-M-pregnene-l7a-ol-3,20-dione acetate(Cpd. No. 47).

EXAMPLE XI The compounds Nos. 44 and 45 were respectively treated by theprocedure of Example V, thus giving correspondingly: 6a-chloro-19,19difluoro-A -pregnadiene- 3,20-dione (Cpd. No.48) and6u-chloro-19,19-difluoro- 7 16oc-methyl-A -pregnadiene-17u-ol-3,20 dioneacetate (Cpd. No. 49).

EXAMPLE XII The compounds Nos. 44 and 45 were respectively treated bythe procedure of Example VI, thus giving correspondingly: 6-chloro19,19-difluoro-A -pregnadiene- 3,20-dione (Cpd. No. 50) and6-ch1oro-19,19-difluoro- 16a methyl-A -pregnadiene 17oc-Ol-3,2O dioneacetate (Cpd. No. 51).

EXAMPLE XIII A solution of 0.17 g. of potassium hydroxide in 0.2 cc. ofwater and 2.5 cc. of methanol was added over 30 minutes to a boilingsolution of 1 g. of 19,19-difluoro-A pregnene-3B,17a-diol-20-one17-acetate (Cpd. No. 19) in 30 cc. of methanol under an atmosphere ofnitrogen. Boiling was continued for a further 2 hours and the solutionwas then cooled, neutralized with acetic acid and concentrated underreduced pressure. Addition of water, followed by crystallization of theprecipitated solid from acetone-hexane, produced 19,19-difluoro-A-pregnene- 3B,17u-diol-20-one (Cpd. No. 52).

Following the same procedure, there were treated the compounds Nos. 20,21, 26, 28, 33, 34, 35, 37, 41, 43, 45, 47, 49 and 51 thus affordingrespectively Cpd. No.:

53. 19,19-dif1uoro-16ot-methy1-A -pre gnene- 35,17a-diol-20-one.

54. 19,19-difluoro-l6fi-methyIA regnene-3B,17a-

diol-ZO-one.

55. 19,19-difluoro-A -pregnene-17u-ol-3,2O-dione.

5 6. 19,19-difluoro-16a-methyl-M-pregnene-17aol-3,20-dione.

57. 19,19-difluor-16fi-rnethyl-A -pregnene-17aol-3,20-dione.

58. 19,19-difluoro-A -pregnadiene-17a-ol- 3,2O-dio-ne.

59. 19,19-difluoro-16a-methyl-A pregnadiene- 17a-ol-3,20-dione.

60. 19,19-difluoro-16,6-methyl-A -pregnadiene- 17a-ol-3,20-dione.

61. 19,19-difiuoro-16ot-methyl-A -pregnadiene- 17u-ol-3,20-dione.

62. 6,8-ch1oro-19,19-difiuoro-16wmethyl-A pregnene-17ot-o1-3,20-dione. I

63. 6p,19,19-trifluoro-16a-methyl-A -pregnene- 17a-ol-3,20-dione.

64. 6a-chloro-19,19-difluoro-16a-methyl-A pregnene-17a-o1-3,20-dione.

65. 6a,19,19-trifluoro-16a-methyl-A -pregnene- 17'a-ol-3,20-dione.

66. 6u-chloro-19,19-difluoro-16u-methyl-A pregnadiene-17a-ol-3,20-dione.

67. 6-chloro-19,19-difiuoro-16a-methyl-A pregnadiene-17a-ol-3,20-dione.

EXAMPLE XIV 1 g. of 19,19-difluoro-16a,17a-isopropy1idenedioxy-Apregnene-3/3-ol-20-one (Cpd. No. 18) was heated on the steam bath with100 cc. of 80% acetic acid under nitrogen for 7 hours, it was thenconcentrated under vacuum to a small volume and poured into water. Theprecipitate was collected, washed well with Water, dried andrecrystallized from acetone-hexane, thus furnishing 19,19-difluoro-Apregnene-3/3,16u,17 x-triol-20-one (Cpd. No. 68).

Following the above procedure, there were treated the compounds Nos. 25and 32 thus affording respectively: 19,19-difluoro-A-pregnene-16a,17a-diol-3,2O-dione (Cpd. No. 69) and 19,19-difluoro-A-pregnadiene-16a,17a-diol- 3,20-dione (Cpd. No. 70).

EXAMPLE XV 72. 19,19-difluoro A -pregnene 17oc-Ol 3,20-dione caproate.

nene-17a-ol-3,20-dione caproate.

74. 19,19-difluoro A -pregnene-3fl,16:,17a-tri0l-20- one tricaproate.

75. 19,19-'difluoro A -pregnene-16d,17a-di01 3,20- dione dicaproate.

EXAMPLE XVI The compounds Nos. 36, 37 and were treated according toExample V, thus yielding respectively: 19,19- difluoro A -pregnatriene3,20-dione (Cpd. No. 76), 19,19-difluoro-16mmethyl-A pregnatriene3,20-dione (Cpd. No. 77) and 6-chloro-19,19-difluoro-16m-methyl- A-pregnatriene-3,20-di-one (Cpd. No. 78).

EXAMPLE XVII The compounds Nos. 32, 69, 70 and 75 were treated inaccordance with Example VI, thus yielding respectively: 19,19-difluoro16a,17a-isopropylidenedioxy A -pregnatriene-3,20-dione (Cpd. No. 79'),19,19-difluoro-A pregnadiene 160:,17a-di0l 3,20-dione (Cpd. No. 80),19,19-difluoro-A -pregnatriene '16a,17u-'diol 3,20- dione (Cpd. No. 81)and 19,19-difluoro-A -pregnadiene- 160c,171xd101-3,20-dl01'16 dicaproate(Cpd. No. 82).

We claim:

1. A, compound of the following formula:

wherein R is a member of the group consisting of hydrogen, hydroxyl anda hydrocarbon carboxylic acyloxy group of less than 12 carbon atoms; Tis selected from the group consisting of hydrogen, a-hydroxyl,a-hydrocarbon I carboxylic acyloxy of less than 12 carbon atoms,a-methyl To a solution of 5 g. of 19,19-difiuoro-A -pregneneand,B-methyl; T and R together are the group wherein R and R each is alower alkyl group; and R is selected from the group consisting ofhydrogen and a hydrocar bon carboxylic acyl group of less than 12 carbonatoms.

2. 19,19-difluoro-A -pregnen-3,B-ol-20 one.

3. 19,19-difluoro-l6a-methyl-A -pregnen-3,B-ol-2O-one.

4. 19,19-difluoro-16fl-methyl-A -pregnen-3,B-ol-20-one.

'5. 19,19-difluoro 16a,17a-isopropylidenedioxy A pregnen-3fi-ol-20 one.

6. 19,19-difluoro-A -pregnen-3fl,17u-diol-20-one 17-acetate.

7. 19,19-difiuo'ro l6ot-methyl-A pregnen 3,8,17owdiol- 20-one17-acetate.

9 8. 19,19-difluoro 16fl-tmethyl-A -pregnen-3fl,17a-diol- 20 one17-acetate.

9. A compound of the following formula:

wherein R is a member of the group consisting of hydrogen, hydroxyl anda hydrocarbon carboxylic acyloxy group of less than 12 carbon atoms; Tis selected from the group consisting of hydrogen, a-hydroxyl,a-hydrocarbon carboxylic acyloxy of, less than 12 carbon atoms, u-methyland fl-methyl; T and R together are the group wherein R and R each is alower alkyl group; Z is selected from the group consisting of a doublebond and a saturated linkage between 0-1 and C-2 and X is a member ofthe group consisting of hydrogen, a-fiuorine, p-fluorine, u-chlorine andB-chlorine.

10. 19,19-difluoro-16a-methyl-A -pregnene-3,ZO-dione. 11.19,19-difluoro-16fimethyl-A pregnene-3,20-dione. 12.19,19-difil1010-16oc,170c isopropylidenedioxy A pregnene-3,20-dione.

13. 19,19-difluoro-A-pregnen-l7a-o1-3,ZO-dione acetate. 14.19,19-difluoro-16a-methyl-A -pregnen 17a o1- 3,20-dione acetate. I 15.19,19-difluoro-16pmethyl-A -pregnen 17a ol- 3,20-dione acetate.

wherein R is a member of the group consisting of hydrogen, hydroXyl anda hydrocarbon carboxylic acyloxy group of less than 12 carbon atoms; Tis selected from the group consisting of hydrogen, a-hydroxyl,u-hydrocarbon carboxylic acyloXy of less than 12 carbon atoms, a-methyland ,B-methyl; T and R together are the group wherein R and R each is alower alkyl group; Z is selected from the group consisting of a doublebond and a saturated linkage between 0-1 and C-2; and X is selected fromthe group consisting of hydrogen, fluorine and chlorine.

No references cited.

- LEWIS GOTTS, Primary Examiner.

THOMAS M. MESHBESHER, Assistant Examiner.

9. A COMPOUND OF THE FOLLOWING FORMULA: